WARNING: RISKS OF LIVER INJURY and TERATOGENICITY
Because of the risk of liver injury and birth defects, Tracleer is available only through a special restricted distribution program called the Tracleer Access Program (T.A.P.), by calling 1 866 228 3546. Only prescribers and pharmacies registered with T.A.P. may prescribe and distribute Tracleer. In addition, Tracleer may be dispensed only to patients who are enrolled in and meet all conditions of T.A.P. [see Warnings and Precautions].
In clinical studies, Tracleer caused at least 3-fold upper limit of normal (ULN) elevation of liver aminotransferases (ALT and AST) in about 11% of patients, accompanied by elevated bilirubin in a small number of cases. Because these changes are a marker for potential serious liver injury, serum aminotransferase levels must be measured prior to initiation of treatment and then monthly [see Dosage and Administration, Warnings and Precautions]. In the postmarketing period, in the setting of close monitoring, rare cases of unexplained hepatic cirrhosis were reported after prolonged (> 12 months) therapy with Tracleer in patients with multiple co-morbidities and drug therapies. There have also been reports of liver failure. The contribution of Tracleer in these cases could not be excluded.
In at least one case, the initial presentation (after > 20 months of treatment) included pronounced elevations in aminotransferases and bilirubin levels accompanied by non-specific symptoms, all of which resolved slowly over time after discontinuation of Tracleer. This case reinforces the importance of strict adherence to the monthly monitoring schedule for the duration of treatment and the treatment algorithm, which includes stopping Tracleer with a rise of aminotransferases accompanied by signs or symptoms of liver dysfunction [see Dosage and Administration].
Elevations in aminotransferases require close attention [see Dosage and Administration]. Tracleer should generally be avoided in patients with elevated aminotransferases (> 3 — ULN) at baseline because monitoring liver injury may be more difficult. If liver aminotransferase elevations are accompanied by clinical symptoms of liver injury (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin ≥ 2 — ULN, treatment with Tracleer should be stopped. There is no experience with the re-introduction of Tracleer in these circumstances.
Tracleer is likely to cause major birth defects if used by pregnant females based on animal data [see Contraindications]. Therefore, pregnancy must be excluded before the start of treatment with Tracleer. Throughout treatment and for one month after stopping Tracleer, females of childbearing potential must use two reliable methods of contraception unless the patient has a tubal sterilization or Copper T 380A IUD or LNg 20 IUS inserted, in which case no other contraception is needed. Hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives should not be used as the sole means of contraception because these may not be effective in patients receiving Tracleer [see Drug Interactions]. Monthly pregnancy tests should be obtained.
Bosentan is the first of a new drug class, an endothelin receptor antagonist.
TRACLEER® is indicated for the treatment of pulmonary arterial hypertension in patients with WHO Class III or IV symptoms, to improve exercise ability and decrease the rate of clinical worsening (see Clinical Studies).
Published Studies Related to Tracleer (Bosentan)
Bosentan in pulmonary hypertension associated with fibrotic idiopathic
interstitial pneumonia. 
receptor antagonist bosentan in this patient group... CONCLUSIONS: This study shows no difference in invasive pulmonary hemodynamics,
BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. [2011.07.01]
RATIONALE: A previous trial of bosentan in idiopathic pulmonary fibrosis (IPF) showed a trend to delayed IPF worsening or death. Also, improvements in some measures of dyspnea and health-related quality of life were observed. OBJECTIVES: To demonstrate that bosentan delays IPF worsening or death... CONCLUSIONS: The primary objective in the Bosentan Use in Interstitial Lung Disease-3 trial was not met. Bosentan was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT 00391443).
Rationale and design of a trial on the role of bosentan in Fontan patients: improvement of exercise capacity? [2011.07]
BACKGROUND: The Fontan circulation is a palliative procedure performed in patients with complex congenital heart disease (CHD), making transpulmonary blood flow dependent on the systemic venous pressure. In a Fontan circulation a low pulmonary vascular resistance (PVR) is crucial, as is epitomized by the observation that a high PVR is a strong predictor of mortality. Long-term follow-up has shown that PVR may rise many years after the Fontan procedure has been performed, possibly due to micro-emboli from a dilated right atrium or from the venous system. Other mechanisms of increased PVR might be aging, obstructed airways caused by lymphatic dysfunction, lack of pulsatile pulmonary flow causing a release of endothelium-derived vasoactive molecules, and prolonged overexpression of vasoconstrictors such as endothelin-1. Mean plasma level of endothelin-1 has been shown to be significantly higher in Fontan patients compared to healthy controls. In patients with pulmonary arterial hypertension (PAH), therapy with bosentan, an endothelin-1 receptor antagonist, has demonstrated to improve exercise capacity and to reduce the elevated PVR. In addition, reduction of PVR is shown early and late after the Fontan procedure on treatment with exogenous NO, another advanced PAH therapy. However, the long term effect of reducing the PVR by bosentan treatment on exercise capacity in Fontan patients is still unknown... CONCLUSION: We hypothesize that treatment with bosentan, an endothelin-1 receptor antagonist, improves maximum exercise capacity and functional capacity in adult Fontan patients. Copyright (c) 2011 Elsevier Inc. All rights reserved.
Tadalafil monotherapy and as add-on to background bosentan in patients with pulmonary arterial hypertension. [2011.06]
BACKGROUND: Tadalafil 40 mg orally once daily, was shown to be well-tolerated and efficacious for pulmonary arterial hypertension in a 16-week, double-blind, placebo (PBO)-controlled trial. Inclusion criteria included the option for background bosentan. Analyses of tadalafil in treatment-naive patients and as add-on to bosentan were pre-specified. Objectives were to provide safety and efficacy data for both groups... CONCLUSION: Tadalafil 40 mg was well-tolerated and provided clinical benefit in patients as monotherapy. It was also well-tolerated when added to background bosentan, but data are insufficient to conclude additional benefit. Copyright (c) 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. [2011.01]
OBJECTIVES: Ischaemic digital ulcers (DUs) are common in patients with systemic sclerosis (SSc) and are a cause of disease-related morbidity. In an earlier trial, treatment with bosentan, an oral endothelin receptor antagonist, reduced the occurrence of new DUs by 48%. The present study (RAPIDS-2, for 'RAndomized, double-blind, Placebo-controlled study with bosentan on healing and prevention of Ischemic Digital ulcers in patients with systemic Sclerosis') was conducted to more fully evaluate the effects of bosentan treatment on DUs associated with SSc... CONCLUSIONS: Bosentan treatment reduced the occurrence of new DUs in patients with SSc but had no effect on DU healing. Bosentan was well tolerated and may be a useful adjunct in the management of patients with SSc with recurrent DUs.
Clinical Trials Related to Tracleer (Bosentan)
BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology [Completed]
This 6-month open label study will evaluate the long term safety of bosentan (via oxygen
saturation) and efficacy (exercise capacity) in patients who have completed the BREATHE-5
study (PAH related to Eisenmenger physiology). Treatment duration is 6 months.
Effects of Tracleer (Bosentan) on Pulmonary Arterial Hypertension Related to Eisenmenger Physiology [Completed]
This study evaluates the effects of bosentan on oxygen saturation, hemodynamics and exercise
capacity in patients with pulmonary arterial hypertension related to Eisenmenger physiology.
Patients receive bosentan or placebo for 16 weeks.
The Effect of Tracleer® on Male Fertility [Completed]
The objective of the study is to evaluate the effects of chronic TRACLEER® treatment on
testicular function via semen analysis in male patients with primary pulmonary arterial
Double Blind, Randomized Trial of Bosentan for Sarcoidosis Associated Pulmonary Hypertension [Recruiting]
Patients with advanced sarcoidosis often develop pulmonary hypertension. Pulmonary
hypertension is a condition where the right side of the heart has to push the blood though
the lungs at a higher pressure than normal. Since this pressure is higher, it is harder for
the heart to pump the blood through the lungs to the left side of the body. If the blood can
not get through the lungs, it can not get pumped through the rest of the body. This leads to
weakness and shortness of breath. This type of hypertension does not usually respond to
regular blood pressure medicines. The purpose of this study is to determine if bosentan
(Tracleer) will help sarcoidosis associated pulmonary hypertension.
Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH) [Recruiting]
This study will investigate the effects of the combination of bosentan and sildenafil.
Patients with symptomatic PAH treated with a stable dose of sildenafil equal to or greater
tha 20 mg t. i.d. for at least 12 weeks will be randomized to placebo or bosentan 125 mg
b. i.d. All randomized patients will be treated with study drug until the predefined target
number of morbidity/mortality events is reached.
Reports of Suspected Tracleer (Bosentan) Side Effects
Pulmonary Arterial Hypertension (398),
Fluid Retention (281),
Oedema Peripheral (259),
Cardiac Failure Congestive (249),
Syncope (249), more >>
Page last updated: 2014-12-01